Ifosfamide With or Without O(6)-Benzylguanine in Treating Patients With Unresectable, Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.

This randomized phase I trial is studying the side effects and best dose of O(6)-benzylguanine when given together with ifosfamide and to see how well it works compared to ifosfamide alone in treating patients with unresectable metastatic solid tumors. Drugs used in chemotherapy, such as ifosfamide and O(6)-benzylguanine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining ifosfamide with O(6)-benzylguanine may kill more tumor cells

Arm II: Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3. Cohorts of 6-12 patients receive escalating doses of BG (administered as a bolus and as a continuous infusion during course 2) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity.

Course 3 and all subsequent courses: All patients receive BG (at the MTD determined in course 2, arm II) and high-dose ifosfamide as in course 2, arm II. In all courses, all patients also receive filgrastim (G-CSF) beginning on day 5 and continuing until blood counts recover. In all courses and in both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Histologically confirmed solid tumor

Unresectable, metastatic disease

No primary tumors

Eligible for high-dose ifosfamide-based therapy

No known brain metastases

Performance status - ECOG 0-1

Performance status - Karnofsky 70-100%

More than 12 weeks

Absolute neutrophil count ≥ 1,500/mm^3

Platelet count ≥ 100,000/mm^3

AST and ALT ≤ 2.5 times upper limit of normal

Bilirubin normal

Creatinine normal

Creatinine clearance ≥ 60 mL/min

No symptomatic congestive heart failure

No unstable angina pectoris

No cardiac arrhythmia

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use effective contraception during and for 4 weeks after study participation

No history of allergic reaction attributed to compounds of similar chemical or biological composition to O6-benzylguanine or other study agents

No concurrent uncontrolled illness

No active or ongoing infection

No psychiatric illness or social situation that would preclude study compliance

More than 24 hours since prior colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF])

No prior hematopoietic stem cell transplantation

No concurrent pegfilgrastim

No concurrent immunotherapy

More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered